The availability of 10 large Utah kindreds with hereditary hemochromatosis provides an opportunity: 1) to establish the mode of inheritance of the disease, 2) to describe the phenotypic expression of the disease in heterozygotes and homozygotes, 3) to establish appropriate diagnostic criteria of the disease, 4) to define the relationship of the hemochromatosis gene to porphyria cutanea tarda and hereditary sideroblastic anemia, and 5) to study the metabolic defect and identify the deficient or aberrant gene product in hemochromatosis. Linkage of the hemochromatosis gene to the HLA locus on chromosome 6 will be pursued by HLA typing the pedigrees. Iron stores will be evaluated by measuring serum iron concentration, transferrin saturation, serum ferritin concentration, urinary iron excretion after deferoxamine, hepatic parenchymal cell stainable iron, and hepatic iron concentration. The handling of iron by cultured human skin fibroblasts will be investigated in an effort to define a cellular metabolic defect which can then be investigated. The possibility that mitochondrial superoxide dismutase is the defcient or aberrant gene product will be examined.